The FDA has posted the warning letter that Teva recently acknowledged getting for its troubled sterile manufacturing plant in Hungary. The letter outlines concerns about sterility and contamination issues at the plant and gives the company a long list of marching orders that it says must be completed before the plant will be allowed to again ship product to the U.S.
Seven observations were listed in the letter including problems with contamination in media fills, a problem the FDA said “indicates a potentially significant sterility assurance problem” at the plant in Godollo that Teva opened in 2012 to expand its sterile manufacturing capacity. The plant is currently closed while Teva works on solving the problems inspectors first outlined in a Form 483 issued in January.
Among problems noted, inspectors said the plant did not adequately investigate media-fill contamination on aseptic manufacturing lines. It cited as an example a media-fill run performed in September of last year which resulted in 31 contaminated units.
It said employees did not identify the microorganisms found in the contaminated units. Identifying them is essential, the FDA said, because otherwise there is no way to sufficiently understand the potential sources and scope of the contamination, the report said.
The FDA criticized the plant for poor aseptic processing techniques including seeing an operator sitting on the clean-room floor during setup of the filling line but then not changing the gown being worn. Others leaned against clean-room walls.
Additionally, investigators said some colony counts for environmental and personnel monitoring did not match up with the plant’s official records. On top of that, there were “quality-related documents in a waste bin” that raised questions about record keeping. Stand-alone computer systems didn’t have controls like routine audit trail reviews and full data retention that would assure that analysts weren’t deleting data.
Teva acknowledged getting the letter two weeks ago and has said that it is working on the problems, addressing “both the specific concerns raised by investigators as well as the underlying causes of those concerns.”
Additionally, Teva said it is working to replenish critical and priority products as quickly as possible, "in some cases by transferring products to other Teva manufacturing sites and--as needed--by identifying alternate suppliers for products in short supply or out of stock.”
The saga at the Godollo site began in January when the FDA inspected the plant, issuing the Form 483. Teva suspended production to deal with the citations, but in May the FDA put the plant on its import alert list, banning all but two drugs: the cancer treatment bleomycin and antibiotic amikacin, which were exempted to avoid shortages. Teva has been recalling its other drugs produced at the facility.
In the letter posted this week, the FDA presented Teva with a list of its expectations, asking among other things for a comprehensive review of all sterility test positive and media-fill failure investigations since January 2014. It wants Teva to update its standard operating procedures and also to review video taken during production of in-date batches sent to the U.S. to figure out what might have caused the contamination.